The possible involvement of nuclear factor (NF)-kappaB in mediating the regulation of interleukin (IL)-6 biosynthesis in response to E. coli-derived lipopolysaccharide-endotoxin (LPS) was investigated in vitro. In alveolar epithelial cells, irreversible inhibition of the proteasome complex by carbobenzoxy-L-leucyl-L-leucyl-L-leucinal (MG-132; 1-50 muM) did not affect LPS-mediated IL-6 secretion. Whereas the selective inhibition of the NF-kappaB pathway by the action of caffeic acid phenyl ethyl ester (CAPE; 1-100 muM) attenuated LPS-dependent IL-6 production at 100 muM, sulfasalazine (SSA, 0.1-10 mM), a potent and irreversible inhibitor of NF-kappaB, did not inhibit LPS-dependent IL-6 secretion. Incorporation of a selectively permeant inhibitor of NF-kappaB, SN-50 (1-20 muM), a peptide which contains the nuclear localization sequence (NLS) for the p50 NF-kappaB subunit and the aminoterminal sequence of Kaposi fibroblast growth factor to promote cell permeability, did not reduce UPS-mediated release of IL-6. These data indicate a NF-kappaB-independent pathway mediating LPS-dependent regulation of IL-6 biosynthesis in the airway epithelium. (C) 2002 Elsevier Science (USA).